The present invention relates to spiro five-membered ring compounds in which the ring which is spiro-connected to the five-membered ring as set forth herein is a saturated bridged or unbridged ring containing one or two nitrogen atoms; to pharmaceutical compositions containing the spiro compounds and to a method for treating diseases of the central and peripheral nervous system using such spiro-compounds or pharmaceutical compositions.
Novel spiro-quinuclidine compounds, in which oxathiolane rings were connected in spiro manner with quinuclidine rings, were described e.g. in European Patent Application No. 0205247 A2, published Dec. 17, 1986, and in U.S. Pat. Nos. 4,855,290 (issued Aug. 8, 1989), 4,981,858 (issued Jan. 1, 1991), 4,900,830 (issued Feb. 13, 1990) and 4,876,260 (issued Oct. 24, 1989). Similarly, some spiro-oxazolines have been described in U.S. Pat. No. 5,053,412 (issued Oct. 5,053,412), while some spiro-oxazolines and some spiro-thiazolines have been described in U.S. Pat. application Ser. No. 07/685,379. It is to be understood that the entire contents of the above-mentioned patents and of U.S. Ser. No. 07/685,379, as well as any other patents and literature articles mentioned in the present patent application are incorporated herein by reference. The novel compounds of the above-mentioned patents were found to possess central nervous system activity. The biological activity of the compound 2-methylspiro(1,3-oxathiolane-5,3)quinuclidine, which exists as geometrical cis- and trans-isomers depending upon whether the 2-methyl group is located on the same side of the oxathiolane ring as the quinuclidine ring nitrogen atom (cis) or on the other side of the quinuclidine ring nitrogen atom (trans), was in particular extensively investigated, and it was found on the basis of pre-clinical tests that the cis- compound (code no. AF102B) was especially promising for the control of senile dementia of Alzheimer's type (SDAT). It is also of interest that each of the cis- and trans-isomers may be optically resolved, and the biological activity of the optical isomers was also investigated in a number of cases.
It is a principal object of the invention to provide novel spiro-compounds. Further objects of the invention, and especially those which relate to the provision of useful pharmaceutical compositions and methods for the treatment of disease, will be apparent from the description which follows.